title: Critical role of nitric oxide in the modulation of prepulse inhibition in Swiss mice.
abstract: BACKGROUND
  Nitric oxide (NO) modulates the dopamine uptake and release processes and appears to be implicated in dopamine-related pathologies, such as schizophrenia. However, it is unclear whether there is excess or deficient NO synthesis in schizophrenia pathophysiology. Analyses of the intracellular pathways downstream of NO system activation have identified the cyclic nucleotide cyclic guanosine monophosphate (cGMP) as a possible target for drug development. Defects in the sensorimotor gating of the neural mechanism underlying the integration and processing of sensory information have been detected across species through prepulse inhibition (PPI).
  
  
  OBJECTIVE
  The aim of this study was to investigate the effects of NO/cGMP increase on sensorimotor gating modulation during dopamine hyperfunction.
  
  
  METHODS
  Mice were treated with NO donors and subjected to the PPI test. Treatment with the NO donor sodium nitroprusside was preceded by pretreatment with a soluble guanylate cyclase (sGC) inhibitor. Additionally, the mice were treated with NO donors and phosphodiesterases inhibitors prior to amphetamine treatment.
  
  
  RESULTS
  Pretreatment with the NO donors enhanced the PPI response and attenuated the amphetamine-disruptive effects on the PPI. The sGC inhibitor did not modify the sodium nitroprusside effects. Additionally, the cGMP increase induced by a specific phosphodiesterase inhibitor did not modify the amphetamine-disruptive effect.
  
  
  CONCLUSIONS
  This study provides the first demonstration that an increase in NO can improve the PPI response and block the amphetamine-disruptive effects on the PPI response. Our data are consistent with recent clinical results. However, these effects do not appear to be related to an increase in cGMP levels, and further investigation is thus required.
authors.affiliation: Departamento de Morfologia, Estomatologia e Patologia Básica, Faculdade de Odontologia, Universidade de São Paulo, 14049-904, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Issy
authors.forename: João Francisco C
authors.initials: JF
authors.lastname: Pedrazzi
authors.forename: Bruno H
authors.initials: BH
authors.lastname: Yoneyama
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Del-Bel
mesh_terms: D000161:Acoustic Stimulation; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D007266:Inhibition, Psychological; D008297:Male; D051379:Mice; D009483:Neuropsychological Tests; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011688:Purinones / Q000494:pharmacology; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology*; D055139:Sensory Gating / Q000187:drug effects / Q000502:physiology*
chemical_list: D015259:Dopamine Agents; D020030:Nitric Oxide Donors; D010726:Phosphodiesterase Inhibitors; D011688:Purinones; D009599:Nitroprusside; D009569:Nitric Oxide; D000661:Amphetamine; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; D006162:Guanylate Cyclase; C011145:zaprinast; D006152:Cyclic GMP